Cysteine-rich secretory protein 1 (CRISP1)

Cysteine-rich secretory protein 1 (CRISP1) is a member of the CRISP family, characterized by 16 conserved cysteine residues and a modular structure including a signal peptide, an N-terminal CAP domain, a hinge region, and a C-terminal cysteine-rich domain (CRD). It is predominantly expressed in the epididymis and secreted into the lumen, where it binds to sperm with two affinities: a loosely bound pool acts as a decapacitation factor and is released during capacitation, while a tightly bound pool remains on sperm for sperm-egg binding and fusion. CRISP1 modulates gamete interactions, sperm motility, and orientation via channel regulation (CatSper and TRPM8), playing a key role in fertilization. Knockouts reveal non-essential but supportive roles in fertility and possible redundancy by other CRISP family members. CRISP1 is proposed as a target for male contraception. Mutations have indirect links to genetic syndromes such as ectodermal dysplasia. No approved drugs target CRISP1 directly.

Other names

AEGL1CRISP-1ARPHUMARPHSCRISP1DHSCRISP1GAEG-like proteinAcidic epididymal glycoprotein homologepididymis secretory protein Li 57HEL-S-57

Physiological inhibitor/blocker of CatSper sperm calcium channel; Modulation of TRPM8 calcium channel activity; Decapacitation factor: prevents premature capacitation by inhibiting signaling cascades in sperm